The overall objective is the determination of basic mechanisms of gene action in spontaneous lymphoma development and progression. The corollary objective is to prevent the development of or arrest the progression of spontaneous lymphomas by over-riding the genetic mechanism. The specific objectives are: 1. To determine the potentialities for differentiation of the neoplastic cells of reticulum cell neoplasms, type B, of strain SJL/J, the reactive host cell components, the influence of gene controlled autoimmunity in spontaneous development and course, and the mechanism of spontaneous regressions and their possible augmentation. 2. To determine the mechanism of action of genes 1 pr, Ai, and the Y chromosome accelerating factor of strain BXSB in autoimmunity and the role of such autoimmunity in the development of reticulum cell neoplasms and thymic lymphoma. 3. To characterize the development of reticulum cell neoplasm, type A of (WB x C57BL/6) F1-an/an hybrids and determine the mechanism of action of mutant gene an in the development of these tumors. 4. To determine the mechanism of action of defective hematopoietic stem cells and defective microenvironment in the development of thymic lymphoma in W and steel locus mutants and the mechamisms of lymphoma prevention by transplants restoring normal stem cells and normal splenic and thymic microenvironments.